The theme of this Center GEEH is "Biochemical and Molecular Mechanisms Underlying Human Variability in Response to Environmental Exposures". The purpose of this NIEHS Center is to provide an administrative infrastructure and technical support to foster the multidisciplinary collaborations necessary to extend basic mechanistic studies on environmental health problems to direct application in human populations, with an emphasis on "gene x environment" interactions. This Center consists of 45 Core Environmental Health Sciences investigators and 37 other investigators involved in Clinical and Translational Sciences research at the UW, organized in 6 areas of research emphasis (AREs): 1) Genomics of Xenobiotic Disposition, 2) Carcinogenesis and Mutagenesis, 3) Susceptible Subpopulations (Children, Elderly and Women), 4) Neurotoxicology, 5) Cardio-pulmonary Toxicology, 6) Biomarkers and Exposure Assessment. The funded research of these core faculty is enhanced by 3 Facility Cores which provide Center investigators access to: 1) Functional Genomics and Proteomics technologies, including high throughput genotyping, microarray analysis and mass spectrometry based proteomics, 2) Exposure Assessment, Biomarkers and Metabolomics Development, 3) an Integrated Environmental Health Sciences Facility Core that includes Bioinformatics &Biostatistics Services and fosters clinical- and population-based research. Through the Director's Discretionary Fund the CEEH also facilitates Technology Access, by providing subsidized access to numerous Shared Resources and Cost Centers at the UW, including techniques such as analytical cytology, histopathology/morphometry, transgenic animal resources, and small animal and molecular imaging. In addition, each year the Pilot Project Program supports 5 exploratory projects that will carry out innovative and novel research related to the theme of the Center. A Community Outreach and Ethics Core provides a mechanism to disseminate important research findings of Center investigators to the general community, as well as a coordinating function to extend and enhance existing community education programs that emphasize issues related to environmental health sciences. ESSENTIAL CHARACTERISTICS STRATEGIC VISION AND IMPACT ON ENVIRONMENTAL HEALTH